The Regulation of Mitochondrial Homeostasis and Metabolism in Pathology: Current data suggest that substrate metabolism and mitochondrial fitness may play a central role in adaptations to pathological stressors in numerous organs. In this project we are evaluating how proteins that control mitochondrial homeostasis and metabolism are both regulated and how they modulate pathologies including: pressure overload and cardiac ischemia in the heart; in immune biology in circulating PBMCs and in brain homeostasis in glial cells. The candidate proteins being currently being explored include Park2 and Sirtuin proteins that appear to be involved in fat metabolism and mitochondrial quality control programs. As human subjects have mutations in both Park2, peripheral blood skin fibroblast samples will be acquired to compare to the metabolic pathways perturbed in murine models.